Usage
- This combination is prescribed for acne vulgaris, particularly inflammatory and comedonal acne, as well as hyperpigmentation disorders like melasma and post-inflammatory hyperpigmentation. It is also used to improve photoaging, including fine lines, wrinkles, and uneven skin tone.
- Pharmacological classification: Azelaic acid is a dicarboxylic acid with keratolytic, comedolytic, anti-inflammatory, antibacterial, and depigmenting properties. Tretinoin is a retinoid, a derivative of vitamin A, classified as a keratolytic and comedolytic agent.
- Mechanism of action: Azelaic acid inhibits tyrosinase, reducing melanin production and lightening hyperpigmented areas. It also exerts antibacterial activity against Cutibacterium acnes (formerly Propionibacterium acnes) and has anti-inflammatory effects. Tretinoin increases epidermal cell turnover, promoting the shedding of dead skin cells and preventing clogged pores. It also reduces inflammation and stimulates collagen production. The combined action of these two agents leads to synergistic effects in treating acne and hyperpigmentation.
Alternate Names
- No commonly used alternate names for the combination itself exist.
- Brand Names: There may be branded formulations containing this combination but no frequently used brand names exist. Usually it is prescribed as individual medications.
How It Works
- Pharmacodynamics: Azelaic acid inhibits the enzyme 5α-reductase. It reduces inflammation and has antimicrobial properties. It also acts as a free radical scavenger, potentially protecting against UV damage. Tretinoin, through binding to retinoic acid receptors in the skin, modulates gene expression, leading to increased cell turnover, normalization of keratinization, decreased inflammation, and stimulation of collagen production.
- Pharmacokinetics: Azelaic acid, when applied topically, has limited systemic absorption (about 3-6%). It is metabolized via beta-oxidation and excreted primarily in the urine. Tretinoin is minimally absorbed through the skin (<5%) and is metabolized in the liver, being excreted in the bile and urine.
- Mode of action: Azelaic acid acts as a tyrosinase inhibitor, thereby decreasing melanin synthesis. It also inhibits the growth of Cutibacterium acnes and reduces inflammation. Tretinoin modulates gene expression by binding to retinoic acid receptors in the skin, leading to normalization of follicular keratinization, decreased inflammation, and increased epidermal cell turnover.
- Elimination pathways: Azelaic acid primarily undergoes renal excretion, and tretinoin is excreted in the bile and urine.
Dosage
Standard Dosage
Adults:
- Apply a thin layer of a formulation containing both medications (typically containing 15-20% azelaic acid and 0.025-0.1% tretinoin), once daily, preferably at night, to the affected areas.
- Start with a lower concentration of tretinoin (0.025%) and gradually increase if tolerated.
- Azelaic acid can be used twice daily.
Children:
- Use is generally not recommended in children under 12 years.
- For adolescents, initiate treatment with lower concentrations and adjust as needed.
Special Cases:
- Elderly Patients: Use with caution. Start with lower concentrations and adjust as needed.
- Patients with Renal Impairment: No specific dosage adjustments necessary for topical azelaic acid. For tretinoin, use with caution.
- Patients with Hepatic Dysfunction: Use with caution. No specific dosage adjustments necessary for topical azelaic acid.
- Patients with Comorbid Conditions: Consider pre-existing skin conditions.
Clinical Use Cases
- This combination primarily treats acne vulgaris and hyperpigmentation disorders. This combination is not indicated in clinical settings like Intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Adjust dosage according to the patient’s tolerance and response. If irritation occurs, reduce the frequency of application or consider lower concentrations.
Side Effects
Common Side Effects
- Dryness, burning, itching, stinging, redness, scaling, and peeling of the skin.
Rare but Serious Side Effects
- Severe irritation, allergic reactions (including hives, swelling, and difficulty breathing), hypopigmentation, especially in individuals with darker skin tones.
Long-Term Effects
- Increased skin sensitivity to sunlight, potential for post-inflammatory hyperpigmentation if acne lesions are not adequately treated.
Adverse Drug Reactions (ADR)
- Severe allergic reactions, worsening of skin conditions.
Contraindications
- Hypersensitivity to azelaic acid or tretinoin, pregnancy (especially for tretinoin). Avoid using topical retinoids, like tretinoin, while breastfeeding.
Drug Interactions
- Other topical acne medications, especially those containing benzoyl peroxide or salicylic acid, can increase irritation.
- Avoid concomitant use of harsh soaps, cleansers, and astringents that can exacerbate skin dryness and irritation.
- Photosensitizing medications can increase the risk of sunburn.
Pregnancy and Breastfeeding
- Pregnancy: Tretinoin is contraindicated during pregnancy due to the risk of teratogenicity. Azelaic acid is generally considered low risk when used topically, but it’s best to discuss with a doctor.
- Breastfeeding: Tretinoin should be avoided during breastfeeding. Azelaic acid is considered low risk when used topically, but ensure the infant’s skin does not come into contact with treated areas.
Drug Profile Summary
- Mechanism of Action: Azelaic acid: inhibits tyrosinase, antibacterial, anti-inflammatory. Tretinoin: increases cell turnover, normalizes keratinization, reduces inflammation.
- Side Effects: Dryness, burning, itching, stinging, redness, peeling. Rarely: allergic reactions, hypopigmentation.
- Contraindications: Hypersensitivity, pregnancy (tretinoin).
- Drug Interactions: Other topical acne medications, harsh soaps, photosensitizing medications.
- Pregnancy & Breastfeeding: Tretinoin contraindicated. Azelaic acid generally considered safe for topical use but consult a doctor.
- Dosage: Apply a thin layer once daily (at night). Adjust concentration as needed.
- Monitoring Parameters: Observe for skin irritation, allergic reactions, and changes in pigmentation.
Popular Combinations
- Not applicable. Generally prescribed as a fixed-dose combination.
Precautions
- General Precautions: Perform a patch test before widespread use. Avoid contact with eyes and mucous membranes. Advise patients to use sunscreen daily.
- Specific Populations: See “Pregnancy and Breastfeeding.”
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azelaic Acid + Tretinoin?
A: Start with a pea-sized amount of a formulation containing 15-20% azelaic acid and 0.025% tretinoin applied once daily, preferably at night. Increase tretinoin concentration (up to 0.1%) as tolerated if necessary.
Q2: Can this combination be used during pregnancy or breastfeeding?
A: Tretinoin is contraindicated in pregnancy. Azelaic acid topical is generally considered low risk, but consult with a doctor. Avoid tretinoin while breastfeeding; azelaic acid topical is generally low risk.
Q3: What are the common side effects?
A: Dryness, burning, itching, stinging, redness, and peeling are common.
Q4: How long does it take to see results?
A: It may take several weeks (6-8 weeks or even longer) to see noticeable improvement.
Q5: Can I use other acne treatments with this combination?
A: Generally, it’s best to avoid using other topical acne treatments concurrently, especially those containing benzoyl peroxide or salicylic acid, as this can increase irritation. Consult with a dermatologist.
Q6: What should I do if I experience excessive irritation?
A: Reduce the frequency of application or use a lower concentration, especially of tretinoin. If irritation persists, discontinue use and consult your dermatologist.
Q7: Is sunscreen necessary when using this combination?
A: Yes, daily sunscreen use is essential, as tretinoin can increase sun sensitivity.
Q8: Can this combination be used to treat acne scars?
A: Tretinoin can help improve the appearance of acne scars over time by promoting collagen production and cell turnover. However, it may not completely eliminate scars.
Q9: How should this combination be stored?
A: Store at room temperature, away from direct sunlight and moisture.
Q10: How should I apply the combination to my skin?
A: Apply a thin layer to clean, dry skin, avoiding the eyes and mucous membranes.
